Therapy For Onychomycosis Research Articles

Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance Imaging.

Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the permeated drug concentration in the deep nail bed is retained above the effective antifungal minimum inhibitory concentration (MIC). We compared the penetration profile of amorolfine and a new topical formula of terbinafine in human mycotic toenails using matrix-assisted laser desorption ionization mass spectrometry imaging-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging. Amorolfine 5% lacquer and terbinafine 7.8% lacquer were applied to mycotic nails (n = 17); nail sections were prepared, and MALDI-FTICR analysis was performed. Based on the MICs of amorolfine and terbinafine needed to kill 90% (MIC90) of Trichophyton rubrum, the fold differences between the MIC90 and the antifungal concentrations in the nails (the multiplicity of the MIC90) were calculated overall and for the keratin-unbound fractions. Both amorolfine and terbinafine penetrated the entire thickness of the nail. The mean concentration across the entire nail section 3h following terbinafine treatment was 1414μg/g of tissue (equivalent to 4.9mM) compared with 780μg/g (2.5mM) following amorolfine treatment (not significantly different; p = 0.878). The median multiplicity of the MIC90 was significantly higher in amorolfine- than terbinafine-treated nails overall (191 vs. 48; p = 0.010) and for the keratin-unbound fractions only (7.4 vs. 0.8; p = 0.002). In this ex vivo study, MALDI-FTICR demonstrated that, although amorolfine 5% and terbinafine 7.8% had similar distribution profiles, both penetrating from the surface to the nail bed, the concentration of amorolfine in the nail was significantly higher than that of terbinafine relative to their respective MIC90 values. Clinical studies are required to determine whether these effects translate to a clinical difference in treatment success.

Rational and Gentle Therapy of Onychomycosis

Diseases caused by microscopic organisms - fungi (incorrectly “molds”) - belong among the most common skin infections and studies show an increasing trend in their occurrence. Dermatomycoses are fungal infections which affect the skin, nails, or hair. Even though the best practices state that naming an infection should be based on identified trigger, the Latin word “tinea” followed by the area of the body (e.g. tinea unguium, tinea pedis) is used more frequently.

Antifungal Selection for the Treatment of Onychomycosis: Patient Considerations and Outcomes.

Onychomycosis, a common fungal nail infection, affects >20% of adults over age 60 and >50% of people over age 70. Onychomycosis may cause pain, psychosocial problems, and secondary infections, therefore meriting treatment. This review describes the range of treatment modalities, including FDA-approved systemic drugs and topical therapies. Additionally, new and emerging oral and topical therapies are discussed. We emphasize the importance of tailoring onychomycosis therapy to individual patient characteristics, comorbidities, preferences, extent of nail involvement, and fungal species, such that physicians may optimize treatment outcomes, patient satisfaction, and safety.

Modern approaches to onychomycosis pharmacotherapy

The authors carried out a research of literary sources in the field of modern methods of onychomycosis therapy. Drugs for topical and systemic therapy, prescribing regimens for systemic antifungal drugs, principles for therapy selections, and indications for the use of systemic antifungals are considered.

Novel Henna-Related Naphthazarine Photosensitizers for an Effective Photodynamic Therapy of Onychomycosis

Novel Henna-Related Naphthazarine Photosensitizers for an Effective Photodynamic Therapy of Onychomycosis

Podology issues: Optimization of onychomycosis therapy

Onychomycosis is an infectious disease of the nail apparatus, caused by pathogenic fungi, manifested in the form of changes in color, configuration of the nail plate, as well as inflammatory processes in the soft tissues adjacent to the nail. Classic therapy in the form of systemic antimycotics is not suitable for everyone (for example, elderly patients with severe liver disorders or concomitant chronic diseases); itraconazole and terbinafine are not combined with a large number of drugs. Therefore, the use of auxiliary non-drug treatment methods becomes extremely important. This article discusses the method of podological treatment of nail plates, proving its effectiveness and safety.

Chronicles of A.I. Pospelov Moscow Society of Dermatovenerologists and Cosmetologists (MSDC was founded on October 4, 1891) Bulletin of the MSDC meeting N 1152

On April 18, 2023, the 1152nd meeting of the Moscow Society of Dermatologists and Cosmetologists named after A.I. Pospelov took place. The meeting was held in a face-to-face format. There were 115 participants in total. Ac-cepted as a member of the MSDC 1 person.
 Two reports are presented in the clinical part of the meeting: clinical variations of the course of skin sarcoidosis: the mini-lecture describes 8 clinical cases of cutaneous sarcoidosis; Kaposi's sarcoma in a 24-year-old patient with positive antibodies to cytomegaly and EpsteinBarr viruses.
 Three reports were presented in the scientific part of the meeting: The possibilities of im-proving the effectiveness of onychomycosis therapy (speaker I.S. Maximov, Sechenov University); The use of botulinum toxin type A for the correction of erythematous-telangiectatic subtype of rosacea (speaker A.O. Yakovleva, State Scientific Center of Dermatovenerology and Cosmetology); A post-graduate student of the Department of Dermatovenereology of the Peoples' Friendship University of Russia Aun Rami Yusefovi made a report on targeted therapy of children with moderate and severe forms of atopic dermatitis (co-speakers ― Prof. E.A. Batkaev, Prof. V.Yu. Ujuhu).

Individual Article: Updated Review of Topical Pharmaceuticals and Complementary and Alternative Medications for the Treatment of Onychomycosis in Both General and Special Populations in the United States.

Onychomycosis is a prevalent condition affecting the United States and global population. Treatment options are limited, with only 3 topical anti-fungal medications garnering approval in the US within the last 25 years: ciclopirox, tavaborole, and efinaconazole. The economic impact and quality of life burden due to onychomycosis are high. Here we provide an up-to-date review of all approved topical anti-fungal therapies for toenail onychomycosis. We discuss treatment efficacies, pharmacology, and use in special populations, as well as current evidence for complementary and alternative medicine.  J Drugs Dermatol. 2023;22:9(Suppl 1):s5-10.

Infrequent laboratory abnormalities during terbinafine therapy for onychomycosis: A retrospective cohort analysis within an integrated health system

Infrequent laboratory abnormalities during terbinafine therapy for onychomycosis: A retrospective cohort analysis within an integrated health system

Onychomycosis Treatment Prescribed at Only Twenty Percent of Visits: A Cross-Sectional Analysis of the National Ambulatory Medical Care Survey 2007 to 2016.

Onychomycosis represents the highest proportion of nail disorders seen in clinical practice. Onychomycosis management may differ amongst specialties, with impact on patient outcomes and quality of life (QoL). We aimed to characterize onychomycosis treatment across specialties, accounting for patient demographics, to assess for potential onychomycosis practice gaps. We conducted a population based cross-sectional analysis using the National Ambulatory Medical Care Survey (NAMCS) 2007 to 2016 (the most recent years available). Overall, 71.6% of onychomycosis visits were with general practitioners (GPs), 25.8% with dermatologists, and 2.58% with pediatricians. No onychomycosis treatment was prescribed at 82.0% of dermatology visits and 78.9% of GP visits. Dermatologists (Odds Ratio (OR):2.27 [95% Confidence Interval (CI):[2.14-2.41]; P<0.0001) and GPs (OR:2.32 [2.21-2.44]; P<0.0001) were more likely than pediatricians to prescribe treatment vs no treatment. Dermatologists were more likely than GPs to prescribe both no treatment vs treatment and topical vs oral antifungals (OR:1.33 [1.16-1.52]; P<0.0001 and OR:4.20 [3.80-4.65]; P<0.0001), respectively. Our study showed that there is a low treatment rate for onychomycosis, with treatment prescribed at only 20% of visits. Untreated onychomycosis might result in secondary infection, pain, and negative QoL impact.1 Although dermatologists are specialists in nail disease management, they saw only about 25% of onychomycosis visits. Future efforts should be directed towards promoting onychomycosis therapy, and educating both patients and referring physicians that dermatologists are primary resources for nail disorder treatment.J Drugs Dermatol. 2023;22(10):1040-1045 doi:10.36849/JDD.6770.

Investigation of active laser delivery and antimycotic activity of zinc-containing nanomaterials and photodynamic drugs in the treatment of onychomicosis

One of the most common nail pathologies is onychomycosis, a fungal nail infection. The low efficiency of existing methods for the treatment of onychomycosis stimulates the search for new drugs and technologies for their delivery under the nail plate. The aim of the investigation was to study the possibility of using Er:YLF laser radiation for sequential laser microporation of the human nail plate and active laser delivery of modern photodynamic preparations and zinc-containing nanomaterials under the nail plate, as well as to determine their antimycotic activity against the Candida albicans fungus under photodynamic exposure with a wavelength of 656±10 nm. A 0.001 % aqueous solution of methylene blue, a chlorine-containing Revixan gel, as well as zinc-containing nanomaterials, which are aqueous solutions of polyvinylpyrrolidone gel with different concentrations of Zn(NO3)2 nanoparticles and acidity, were studied. It was established that the smallest number of laser pulses required for in vitro microporation of the nail plate and active laser delivery under the nail plate is required when using a 0.001 % aqueous solution of methylene blue, and the largest is required when using Revixan gel. For zinc-containing nanomaterials, an increase in the concentration of Zn(NO3)2 nanoparticles from 14 to 40 % leads to an increase in the number of laser pulses required for active drug delivery under the nail plate by 1.25 times, while a change in the acidity of the pH gel from 7.0 to 6.7 does not has a significant impact on it. It was found that all the studied drugs in combination with photodynamic action at a wavelength of 656±10 nm have an antimycotic effect on the Candida albicans fungus culture. The minimum growth rate of Candida albicans colonies was observed when using the Revixan gel, for which the antimycotic activity reached 73.8 %. The obtained results can be applied in the development of laser systems and technologies for the treatment of fungal diseases, including for photodynamic therapy of onychomycosis.

A Bibliometric Analysis of the Top 100 Highly Cited Onychomycosis Publications Using SCOPUS Database (1972–2022)

Introduction: Onychomycosis represents half of nail disorders seen in clinical practice. Despite its high prevalence, a bibliometric analysis has not been performed. We aimed to identify the top 100 highly cited onychomycosis publications over the last 50 years to better understand research trends. Methods: SCOPUS was searched for onychomycosis publications, using “onychomycosis” and “nail fungus” 1/1/1972-12/31/22 on 3/25/23. Top 100 highly cited publications were recorded and ranked by total citation count. Results: Total citation count was 13,456, with the top 10 articles with highest citation count/year having average 28.7 citations/year. Most articles were published in high IF journals. From 1982 to 2011 (no treatment articles – 1972–1981), there was an 8.6% increase in articles discussing treatment. Overall, 42% of first authors were female. Conclusion: We found an overall increase in articles discussing onychomycosis therapies over time, with the majority published in high IF journals. We also found a relatively greater percentage of female first authors compared to studies on other dermatologic topics. While total citation count remains a widely used metric of impact in bibliometric studies, average citation count/year may be a better measure of impact and should be considered in future studies.

Erythema Nodosum Associated with Terbinafine Therapy- A Case Report

Terbinafine is a commonly used anti-fungal agent in dermatological practice but not one clearly associated with erythema nodosum. There is only one published report in 2014 that described a delayed onset of erythema nodosum after cholestasis complicated terbinafine therapy. We report the case of a woman who developed erythema nodosum whilst on terbinafine therapy for onychomycosis to further consider this link and its potential implications.

Onychomycosis guideline update

Self-medication with antimycotic nail polishes plays an important role in Germany due to the numerous OTC drugs available and an increasing number of onychomycosis cases. Older patients in particular are more frequently affected due to slower nail growth and the possible existence of predisposing diseases [1]. But the prevalence is also increasing in children [2]. This makes guideline-based recommendations regarding diagnosis, therapy and prophylaxis of onychomycosis all the more important.

Nail Society of India (NSI) Recommendations for Pharmacologic Therapy of Onychomycosis.

Onychomycosis (OM) is the commonest cause of dystrophic nails, responsible for upto 50% of cases. Apart from significantly damaging the nails, quality of life, and self-image of the sufferer, it also acts as a reservoir of fungal infections carrying important implications for emerging recalcitrant dermatophytoses. Treatment of OM is based on guidelines released almost a decade back, in addition to published literature and personal preferences. Hence, an expert group of nail society of India (NSI) worked towards drafting these guidelines aimed at compiling recommendations for pharmacologic treatment of OM, based on scientific evidence, along with practical experience. The group did an extensive analysis of available English language literature on OM published during the period 2014-2022. The evidence compiled was graded and discussed to derive consensus recommendations for practice. Special focus was placed on combination therapies and adjunct therapies, including experience of members, to improve treatment outcomes.

Formulation and Evaluation of Nail Drug Delivery System of Anti Fungal Drug

The purpose of this study was to prepare nail lacquer for nail drug delivery system of anti fungal drug in order to improve the physicochemical parameters that influence the drug permeation through a nail plate to reach the systemic circulation and the neighbouring target sites. The success of local topical therapy for onychomycosis depends on the achievement of effective chemical concentrations into/through the human nail plate; therefore, a suitable antifungal drug must be coupled with an appropriate delivery method. The method should maximize the effect of the active principle by aiding its diffusion into the nail bed to levels exceeding the minimum inhibitory concentration (MIC) against local infection by dermatophytes. Thus, a suitable carrier may be needed to enhance drug penetration through the nail barrier.
 The nail lacquer formulations were prepared by simple mixing method and analyzed for non volatile content, gloss, smoothness to flow, drug diffusion studies, and % drug content. Among all formulations, nail lacquer prepared with 2% oxiconazole, 6% nitrocellulose, 1% ethyl cellulose, 15% salicylic acid, 10% propylene glycol and 10% 2-H β-CD exhibited good non volatile content, drug release, drug content estimation and zone inhibition i.e. F4 formulation. The drug release profiles were achieved 93.2% at 12 h. The in vitro ungual permeation studies revealed a good in vitro in vivo correlation. Nail lacquer were substantially stable after 1 month storage at 40±2℃.

Fractional CO2 laser - assisted methylene blue photodynamic therapy is a potential alternative therapy for onychomycosis in the era of antifungal resistance

BackgroundTreatment of onychomycosis is challenging by virtue of the impact of nail disfigurement, the location of the fungi within the nail and reported antifungal resistance worldwide. Light-based technologies are promising primary or adjunctive therapeutic modalities. We aimed to compare the efficacy of photodynamic therapy and fractional CO2 laser monotherapy either alone or in combination for onychomycosis. Patients and methodsThis prospective randomized comparative study was conducted on 51 onychomycosis patients divided into three groups. In group A, patients were treated using 6 photodynamic therapy sessions using methylene blue and IPL (560 to 700 nm, fluence 12 J/cm2). Group B patients were treated using 6 bimonthly fractional CO2 laser sessions (10,600 nm, 1.600 mj energy and 0.6 mm density) and group C patients were treated using 6 combined fractional CO2 laser and photodynamic therapy sessions. Patients were evaluated mycologically, dermoscopically and clinically by calculation of proximal nail diameter percentage at baseline, monthly, at the end of treatment and after a 6‐month follow‐up period post-treatment. ResultsCandida was the most commonly isolated organismin in 64.7%, 70.6% and 70.6% of the pateints in groups A, B and C, respectively. The dermoscopic findings in the total dystrophic onychomycosis was subungual hyperkeratosis in 6 patients (100%), longitudinal streaks and striae in 1 patient (16.7%). In dorsolateral subungual onychomycosis, jagged proximal edge in 31 patients (70.5%), and pigmentation in 30 patients (68.2%) were noted. In proximal subungual onychomycosis irregular matt patches were seen in 1 patient (100%). Proximal nail diameter percentage showed statistically significant improvement after treatment and 6 months follow up in the 3 studied groups. Mean increase of proximal nail diameter after treatment was highest in group C (52.94 ± 20.24), followed by group B (43.82 ± 21.03) and least in group A (35.29 ± 17.0). This difference was statistically significant (p = 0.044). Reported side effects were mild-moderate pain, discoloration and paronychia. ConclusionWe conclude that fractional CO2 laser and photodynamic monotherapy, and their combination achieve high success rates, good patient satisfaction and safety profile. Fractional CO2-assisted photodynamic therapy is associated with the highest improvement over either fractional CO2 or photodynamic therapy alone.

A randomized comparative study of fractional carbon dioxide laser-assisted drug delivery with amorolfine versus amorolfine alone for the treatment of onychomycosis

Objective The study was done to compare the clinical efficacy rate, patient satisfaction, and side effects of fractional carbon dioxide (CO2) laser-assisted topical therapy with amorolfine versus amorolfine alone for the treatment of onychomycosis. Patients and methods In all, 100 patients were recruited for the study and were divided based on the lottery system into two groups. Group 1 (50 patients) received a combination of fractional CO2 laser and topical amorolfine (5%) and group 2 (n=50) received 5% amorolfine alone. The overall treatment efficacy was determined using clinical examination, onychoscopic pattern, and mycological clearance by comparing the infected area at baseline and 12 weeks after last treatment. Results Compared with group 2, clinical efficacy rate was significantly more in group 1 (22 vs. 0%, P<0.0001). Patient satisfaction rate was also higher in group 1 (64 vs. 6%, P<0.0001). Among the side-effects, mild pain was noted in group 1 with none in group 2 patients. Conclusion Fractional CO2 laser-assisted delivery of topical amorolfine (5%) therapy of onychomycosis showed a better clinical response than topical amorolfine (5%) alone. Fractional CO2 lasers may be explored further for use by standardizing the parameters and number of sessions to achieve better cure rates and thereby can replace systemic treatment.

Response surface methodological approach for optimization of photodynamic therapy of onychomycosis using chlorin e6 loaded nail penetration enhancer vesicles.

Antimicrobial photodynamic inactivation (aPDI) has a tremendous potential as an alternative therapeutic modality to conventional antifungals in treatment of onychomycosis, yet the nail barrier properties and the deep-seated nature of fungi within the nails remain challenging. Therefore, the aim of this study was to prepare, optimize, and characterize Chorin e6 (Ce6) nail penetration enhancer containing vesicles (Ce6-nPEVs) and evaluate their photodynamic mediated effect against Trichophyton rubrum (T.rubrum); the main causative agent of onychomycosis. Optimization of the particle size and encapsulation efficiency of nPEVs was performed using a four-factor two-level full factorial design. The transungual delivery potential of the selected formulation was assessed in comparison with the free drug. The photodynamic treatment conditions for T.rubrum aPDI by free Ce6 was optimized using response surface methodology based on Box-Behnken design, and the aPDI effect of the selected Ce6-nPEVs was evaluated versus the free Ce6 at the optimized condition. Results showed that formulations exhibited high encapsulation efficiency for Ce6 ranging from 79.4 to 98%, particle sizes ranging from 225 to 859nm, positive zeta potential values ranging from +30 to +70mV, and viscosity ranging from 1.26 to 3.43cP. The predominant parameters for maximizing the encapsulation efficiency and minimizing the particle size of Ce6-nPEVs were identified. The selected formulation showed 1.8-folds higher nail hydration and 2.3 folds improvement in percentage of Ce6 up-taken by nails compared to the free drug. Results of the microbiological study confirmed the reliability and adequacy of the Box-Behnken model, and delineated Ce6 concentration and incubation time as the significant model terms. Free Ce6 and Ce6-nPEVs showed an equipotent in vitro fungicidal effect on T.rubrum at the optimized conditions, however Ce6-nPEVs is expected to show a differential effect at the in vivo level where the advantage of the enhanced nail penetration feature will be demonstrated.

Fabrication and Characterization of Tolnaftate Loaded Topical Nanoemulgel for the Treatment of Onychomycosis

The core objective of this work was to formulate nanoemulgel containing tolnaftate loaded for sustained delivery of the treatment of onychomycosis. Onychomycosis was not regarded as a serious infection until quite recently. The oral antifungal therapy for onychomycosis usually lasts long and brings a set of adverse effects, especially hepato-toxicity and drug interactions. The incidence of onychomycosis in with more prevalent in warm humid climates topical therapy is usually prescribed only in mild cases. It prevails among around 5% of the total world population and affects toenails much more than fingernails. The incidence of onychomycosis with more prevalent in warm humid climates so an attempt has been made to develop nanoemulsion containing tolnaftate. Formulations were optimized by factorial design. Developed formulations were evaluated and characterized for drug content-96.72, in-vitro release study-68.42%, SEM study. Based on the drug content, in-vitro release study, and SEM study, the optimized formulation was converted into nanoemulgel. The developed topical nanoemulgel was evaluated for the determination of pH 6.60, determination of spreadability 17.77 g.cm/sec, measurement of viscosity 12350 cp, drug content Study 96.52%, in-vitro drug release study 70.42% found to be effective and producing a sustained effect.